Hemoglobinopathies are a major case of morbidity and premature mortality worldwide. With an estimated over 10,000 live birth each year of infants with Thalassemia major and 5,200 live births of infants with sickle cell disease each year, hemoglobinopathies have emerged as a major public health problem in India. Newborn screening (NBS) can dramatically reduce morbidity and mortality from sickle cell disease (SCD) by facilitating early initiation of penicillin prophylaxis and enrollment in comprehensive care. However, NBS for hemoglobinopathies or other genetic and metabolic diseases has primarily been implemented in highly structured health systems in developed countries. In India, SCD is most prevalent in indigenous populations classified as scheduled tribes who have a high prevalence of socioeconomic disadvantage and who live in rural or forested regions. Gujarat state with large population of scheduled tribes is the first state to initiate a comprehensive hemoglobinopathies program. This project is a Indo-US collaboration between investigators at Children's Hospital of Pittsburgh and Children's hospital of Oakland and the Institute of Immunohematology, Mumbai and Valsad Raktadan Kendra and Gujarat State sickle cell disease treatment and control program, Valsad to pilot newborn screening for hemoglobinopathies in South Gujarat. Specific aims are 1. Test the feasibility of establishing a newborn screening and follow-up program for sickle cell disease in the tribal regions of south Gujarat. 2. Determine the feasibility of enrolling asymptomatic infants diagnosed with sickle cell disease in comprehensive care and 3. Examine the acceptability of newborn screening follow-up and genetic testing and counseling for hemoglobinopathies detected on NBS. We will combine high throughput laboratory screening methods, systematic follow-up, standardized clinical care, integrated laboratory and child health informatics system for tracking patient care, telecommunication to bypass gaps in infrastructure and socio- behavioral studies to determine the feasibility, efficacy and acceptability of NBS and follow-up for hemoglobinopathies. NBS will be targeted to the indigenous peoples of the scheduled tribes, in this region who have a very high carrier frequency of hemoglobinopathies, live in semi-urban, rural or forested regions, are frequently mobile and have high prevalence of socioeconomic disadvantage. Results of these studies will provide the basis for developing universal newborn screening, and comprehensive care for hemoglobinopathies, India. This will also serve as a model for NBS for other genetic and metabolic disorders in India, as well as generate insights that may be useful in the delivery of primary health care to disadvantaged sections and disease management programs for other chronic disorders. Sickle cell disease is an inherited disorder of hemoglobin which can be rapidly fatal in infancy be cause of infection by a bacterium called pneumococcus. Screening of newborns for this disease leads to early diagnosis and initiation of prophylaxis with penicillin and comprehensive care and a dramatic reduction in suffering and early death from this disease. In this collaboration with investigators from India and the USA we propose to adapt a successful model of newborn screening in the USA to pilot newborn screening and comprehensive care for sickle cell disease among a rural disadvantaged indigenous population in Gujarat State of India.